The proposed research is intended to explore the physiological and biochemical activities necessary for platelet adherence to collagen. The interaction of platelets with collagen will be assessed by affinity chromatography on collagen/Sepharose. The studies to be done will focus on the role of cyclic nucleotides, membrane proteins, and contractility in mediating or promoting platelet-collagen adherence. The role of cyclic nucleotides will be studied by determining the effect on adherence of agents that alter the cellular levels of cyclic AMP and cyclic GMP and by measuring changes in platelet cyclic AMP content before and after adherence. The role of membrane proteins will be studied using penetrating and non-penetrating sulfhydryl inhibitors. The role of contractility will be assessed using inhibitors of platelet contractile proteins. In other studies, analysis will be made of the effect, if any, of the platelet aggregating factor in diabetic plasma to promote platelet adherence to collagen. The results of the studies will provide a more detailed understanding of the conditions which promote platelet-collagen interaction and will define the usefulness of affinity chromatography in identifying conditions promoting platelet hyperresponsiveness to stimuli.